This project is aimed at understanding the biochemistry, biology and molecular pathogenesis of aging in the nervous system. By far the most common neuronal degenerations that accompany aging are the Alzheimer's type presenile and senile dementia (SDAT). In this disease the most widespread and specific pathological pictures are the presence of neurofibrillary tangles at light microscopic or paired helical filaments at electromicroscopic level. For these reasons, we propose to isolate and biochemically characterize the paired helical filamentous proteins. We will focus on the comparison of the paired helical filaments, neurofilaments, tubulin, and actin of the brain. We will also investigate the relationship between PHF and a brain soluble protein, neuronin S-6, which is found to decrease in the demented brain. Finally, we will purify and characterize the non-neural fibrous proteins of normal and Alzheimer patients as a function of age. We will use such techniques as neuronal cell isolation, subcellular fractionation, immunodiffusion, radioimmunoassay, gel electrophoresis, peptide mapping, immunohistochemistry and electronmicroscopy to understand the role of fibrous proteins in aging of the brain.